Green tea polyphenol (−)-epigallocatechin-3-gallate triggered hepatotoxicity in mice: Responses of major antioxidant enzymes and the Nrf2 rescue pathway

Wang, Dongxu; Wang, Yijun; Wan, Xiaochun; Yang, Chung S.; Zhang, Jinsong

doi:10.1016/j.taap.2014.12.018

Cited by 138 publications

(115 citation statements)

References 38 publications

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“…6A) nor caused hepatotoxicity as indicated by the normal serum levels of ALT, AST and 4-HNE (Table 2), as well as hepatic γ-H2AX protein (Fig. 6C) whose expression has been demonstrated to be dramatically increased during the EGCG-triggered liver injury [33], [34], [35], [36]. The EGCG treatment actually decreased the inflammation as evidenced by the lower levels of serum IL-2 and IL-10 (Table 2).…”

Section: Resultsmentioning

confidence: 84%

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Epigallocatechin-3-gallate enhances key enzymatic activities of hepatic thioredoxin and glutathione systems in selenium-optimal mice but activates hepatic Nrf2 responses in selenium-deficient mice

Dong

Wang

et al. 2016

Redox Biology

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Selenium participates in the antioxidant defense mainly through a class of selenoproteins, including thioredoxin reductase. Epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active catechin in green tea. Depending upon the dose and biological systems, EGCG may function either as an antioxidant or as an inducer of antioxidant defense via its pro-oxidant action or other unidentified mechanisms. By manipulating the selenium status, the present study investigated the interactions of EGCG with antioxidant defense systems including the thioredoxin system comprising of thioredoxin and thioredoxin reductase, the glutathione system comprising of glutathione and glutathione reductase coupled with glutaredoxin, and the Nrf2 system. In selenium-optimal mice, EGCG increased hepatic activities of thioredoxin reductase, glutathione reductase and glutaredoxin. These effects of EGCG appeared to be not due to overt pro-oxidant action because melatonin, a powerful antioxidant, did not influence the increase. However, in selenium-deficient mice, with low basal levels of thioredoxin reductase 1, the same dose of EGCG did not elevate the above-mentioned enzymes; intriguingly EGCG in turn activated hepatic Nrf2 response, leading to increased heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 protein levels and thioredoxin activity. Overall, the present work reveals that EGCG is a robust inducer of the Nrf2 system only in selenium-deficient conditions. Under normal physiological conditions, in selenium-optimal mice, thioredoxin and glutathione systems serve as the first line defense systems against the stress induced by high doses of EGCG, sparing the activation of the Nrf2 system.

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Section: Resultsmentioning

confidence: 84%

“…for 5–7 days in Kunming mice, which are also used herein, did not generate a comprehensive Nrf2 response in the liver of Se-adequate mice [33], [34]. Therefore, we next investigated whether the robust Nrf2 response as seen in the Se-deficient mice was associated with the EGCG-triggered hepatotoxicity.…”

Section: Resultsmentioning

confidence: 99%

Epigallocatechin-3-gallate enhances key enzymatic activities of hepatic thioredoxin and glutathione systems in selenium-optimal mice but activates hepatic Nrf2 responses in selenium-deficient mice

Dong

Wang

et al. 2016

Redox Biology

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“…Indeed, in correlation with the mentioned beneficial effects of green tea, a large body of evidence indicates that its extract can induce both antioxidant and prooxidant activities, which depends on the biological conditions and the dosage. (10). Animal model studies showed that higher doses of EGCG induced pro-inflammatory responses, hemorrhagic lesions in stomach and intestine, oxidative stress in liver cells, enzyme rise, and acute hepatitis.…”

Section: Discussionmentioning

confidence: 99%

“…Green tea contains a mixture of catechin polyphenols and caffeine, which both play an important role in weight-loss and weight maintenance (9). It is noteworthy that in addition to its anti-obesity properties, several favorite effects are supposed for this plant including relaxation, cardiovascular protection, neuroprotection, anti-oxidant, anticancer, anti-inflammatory, and anti-thrombogenic effects (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

The Anti-Obesity Effects of Green Tea: A Controlled, Randomized, Clinical Trial

Nabi¹,

Sedighinejad²,

Haghighi³

et al. 2018

Iran Red Crescent Med J

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Background: Obesity is a global health threatening issue with increasing prevalence in the developed and developing world. The limited efficacy and side effects of conventional treatments motivated the researchers to look for novel, safe, and effective therapeutic strategies. Objectives: The current study aimed at investigating the anti-obesity effects of green tea in a population in North of Iran. Methods: The current single-blind, placebo-controlled, parallel, clinical trial was conducted in Guilan outpatient clinic in Rasht, Iran, from January to December 2015. Eligible subjects were randomly allocated into 2 groups of green tea and control. In the GT Group, a cup of green tea and in the C group an equal amount of mineral water was taken 30 minutes after breakfast and lunch. The outcomes including body weight (BW), body mass index (BMI), hip circumference, waist circumference, and waist-to-hip ratio were measured at baseline, as well as 8 and 12 weeks after the intervention (T0,T_1, T_2).Results: Finally, data obtained from 84 cases in groups GT (n = 41) and C (n = 43) were analyzed. No significant difference was observed in terms of baseline demographics and measurements between the 2 groups including male/female (P = 0.766), age (P = 0.376), weight (P = 0.846), height (P = 0.413), waist circumference (P = 0.619), hip circumference (P = 0.619), and waist-to-hip ratio (P = 0.301). According to the intragroup analyses, the trend of changes from baseline to 12 weeks after intervention were significant in both groups (P = 0.001); BW (79.88 ± 7.06 to 72.44 ± 6.82 kg) and (80.21 ± 7.16 to77.07 ± 7.22 kg) , BMI (29.95 ± 1.79 to 26.86 ± 2.59 kg/m 2 ) and (29.69 ± 2.1 to 27.07 ± 2.22 kg/m 2 ) , waist circumference (87.77±6.06 to 83.913 ± 6.13 cm) and (86.94 ± 8.05 to 85.23 ± 7.89 cm), and hip circumference (102.41 ± 7.35 to 98.3 ± 7.54 cm) and (101.02 ± 8.47 to 99.31 ± 8.81 cm) in GT and C groups, respectively. However no such difference was observed in waist/hip ratio in the GT and C groups (P = 0.087) and (P = 0.322), respectively. A significant difference was observed at T1 (P = 0.024 and P = 0.025) and T2 (P = 0.025 and P = 0.006), according to weight and BMI, respectively. However, the differences were not statistically significant based on the other variables. Conclusions: Green tea could be a safe and effective choice for patients with obesity. However, further well-designed trials are required to confirm these findings.

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“…EGCG also showed a protective effect against oxidative stress-induced cerebral ischemia through Nrf2/ARE activation [62]. EGCG suppressed the Nrf-2 pathway in a lethal dose with biphasic dose-response effect in mice hepatocytes [63]. EGCG has been shown to inhibit oxidative stress damage induced by HO-1 through Nrf2 in HUVECs with ambient fine particulate matter (≤2.5 μm in aerodynamic diameter PM2.5) [64].…”

Section: Epigallocatechin Gallatementioning

confidence: 99%

Stress Response of Dietary Phytochemicals in a Hormetic Manner for Health and Longevity

Gezer¹

2018

Gene Expression and Regulation in Mammalian Cells - Transcription Toward the Establishment of Novel Therapeutics

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The stress responses observed in mammalian cells can be classified as heat shock response, unfolded protein response, autophagic response, deoxyribonucleic acid damage response, antioxidant response, and sirtuin response at the intracellular and molecular levels. Factors that strengthen the hemodynamic structure causing low-level molecular damage and activating one or several stress response pathways are called hormetins. Hormetins can be categorized as physical, physiological, biological, and nutritional hormetins. Nutritional hormetins provide an interesting, comprehensive research topic because of their effects on health and lifespan. Dietary phytochemicals, with their low-level stress-inducing effects, are potential nutritional hormetins. Resveratrol, curcumin, epicatechin, isothiocyanates, ferulic acid, and certain vitamin-minerals can induce a heat shock response, unfolded protein response, autophagic response, deoxyribonucleic acid damage response, antioxidant response, and sirtuin response causing the stimulation of kinases and transcription factors. Studies have shown that these phytochemicals are related to nuclear factor-erythroid 2, sirtuins, nuclear factor-kappa B, and heat shock response pathways. In this chapter, the stress response of dietary phytochemicals will be systematically examined in a hormetic manner for delay of age-related diseases, healthy aging, and longevity based on current data.

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Green tea polyphenol (−)-epigallocatechin-3-gallate triggered hepatotoxicity in mice: Responses of major antioxidant enzymes and the Nrf2 rescue pathway

Cited by 138 publications

References 38 publications

Epigallocatechin-3-gallate enhances key enzymatic activities of hepatic thioredoxin and glutathione systems in selenium-optimal mice but activates hepatic Nrf2 responses in selenium-deficient mice

Epigallocatechin-3-gallate enhances key enzymatic activities of hepatic thioredoxin and glutathione systems in selenium-optimal mice but activates hepatic Nrf2 responses in selenium-deficient mice

The Anti-Obesity Effects of Green Tea: A Controlled, Randomized, Clinical Trial

Stress Response of Dietary Phytochemicals in a Hormetic Manner for Health and Longevity

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